This chapter focuses on cell-based and gene-based therapies that could replace damaged dopamine neurons in Parkinson's disease (PD), restore their function, or obviate their consequences. Such treatments offer the potential of restoring dopamine innervation to the striatum and other brain regions in a more physiological manner than can be accomplished with standard levodopa therapy, providing enhanced benefits without motor complications. These types of therapies might provide the maximal benefits of levodopa without motor complications and might theoretically have downstream effects on nondopaminergic areas that are affected in PD. Clinical trials have been performed with each of these classes of therapies discussed in the chapter. The concept underlying cell-based therapies is that implantation of dopaminergic cells into the denervated striatum of a PD patient might compensate for the loss of cells that occurs as a part of the disease process. Gene-based therapy involves the use of a viral vector to deliver the DNA or RNA of the therapeutic protein. The chapter discusses fetal nigral transplantation, stem cells, and other cell-based therapies. As with cell-based therapies, it is important to consider that current approaches to gene therapy are not likely to improve the nondopaminergic features of PD, and long-term success may depend on developing approaches that can accomplish this goal.